The serum of Reye's Syndrome patients has been shown to have unusual effects on rat liver mitochondria in vitro. This activity suggested the presence of a "serum factor" which might be important in the pathogenesis of the illness in children. The objectives of this project are to ascertain the mechanism of action of the factor, to determine the chemical identity of the factor, and to evaluate its potential role as a diagnostic or prognostic marker. The factor appears to be of small molecular weight, and to interact with the terminal cytochromes of the respiratory chain. We have found serum factor activity to be present at low levels in the normal population, and markedly elevated during the acute phase of Reye's Syndrome. The activity remains elevated in fatal cases, but decreases to normal levels during convalescence in survivors. In the coming year, the primary objective will be to determine the chemical identity of the unknown factor and to further assess its possible pathogenic role in the illness.